IL1AP_MACMU
ID IL1AP_MACMU Reviewed; 570 AA.
AC P59822;
DT 22-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 22-AUG-2003, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Interleukin-1 receptor accessory protein;
DE Short=IL-1 receptor accessory protein;
DE Short=IL-1RAcP;
DE EC=3.2.2.6 {ECO:0000255|PROSITE-ProRule:PRU00204};
DE Flags: Precursor;
GN Name=IL1RAP;
OS Macaca mulatta (Rhesus macaque).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9544;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ALTERNATIVE SPLICING, AND
RP CHARACTERIZATION OF ISOFORM 2.
RX PubMed=12530978; DOI=10.1016/s1074-7613(02)00514-9;
RA Smith D.E., Hanna R., Friend D., Moore H., Chen H., Farese A.M.,
RA MacVittie T.J., Virca G.D., Sims J.E.;
RT "The soluble form of IL-1 receptor accessory protein enhances the ability
RT of soluble type II IL-1 receptor to inhibit IL-1 action.";
RL Immunity 18:87-96(2003).
CC -!- FUNCTION: Coreceptor for IL1RL2 in the IL-36 signaling system (By
CC similarity). Coreceptor with IL1R1 in the IL-1 signaling system.
CC Associates with IL1R1 bound to IL1B to form the high affinity
CC interleukin-1 receptor complex which mediates interleukin-1-dependent
CC activation of NF-kappa-B and other pathways. Signaling involves the
CC recruitment of adapter molecules such as TOLLIP, MYD88, and IRAK1 or
CC IRAK2 via the respective TIR domains of the receptor/coreceptor
CC subunits. Recruits TOLLIP to the signaling complex. Does not bind to
CC interleukin-1 alone; binding of IL1RN to IL1R1, prevents its
CC association with IL1R1 to form a signaling complex. The cellular
CC response is modulated through a non-signaling association with the
CC membrane IL1R2 decoy receptor. Coreceptor for IL1RL1 in the IL-33
CC signaling system (By similarity). Can bidirectionally induce pre- and
CC postsynaptic differentiation of neurons by trans-synaptically binding
CC to PTPRD (By similarity). May play a role in IL1B-mediated
CC costimulation of IFNG production from T-helper 1 (Th1) cells (By
CC similarity). {ECO:0000250|UniProtKB:Q61730,
CC ECO:0000250|UniProtKB:Q9NPH3, ECO:0000269|PubMed:12530978}.
CC -!- FUNCTION: [Isoform 2]: Associates with secreted ligand-bound IL1R2 and
CC increases the affinity of secreted IL1R2 for IL1B; this complex
CC formation may be the dominant mechanism for neutralization of IL1B by
CC secreted/soluble receptors (PubMed:12530978). Enhances the ability of
CC secreted IL1R1 to inhibit IL-33 signaling (By similarity).
CC {ECO:0000250|UniProtKB:Q61730, ECO:0000269|PubMed:12530978}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + NAD(+) = ADP-D-ribose + H(+) + nicotinamide;
CC Xref=Rhea:RHEA:16301, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17154, ChEBI:CHEBI:57540, ChEBI:CHEBI:57967; EC=3.2.2.6;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00204};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16302;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00204};
CC -!- SUBUNIT: The interleukin-36 receptor complex is a heterodimer of IL1RL2
CC and IL1RAP; the association is inhibited by IL36RN (By similarity). The
CC interleukin-1 receptor complex is a heterodimer of IL1R1 and IL1RAP.
CC Associates with IL1R2 to form a non-signaling interleukin-1 receptor
CC complex. Interacts with IL-33-bound IL1RL1 to form the minimal
CC interleukin-33 signaling complex with a 1:1:1 stoichiometry. Interacts
CC with KIT (independently of stimulation with KITLG/SCF). A mast cell-
CC specific KITLG/SCF-induced interleukin-33 signaling complex contains
CC IL1RL1, IL1RAP, KIT and MYD88 (By similarity). Interacts (via the first
CC immunoglobilin domain) with PTPRD (via the third immunoglobilin
CC domain); induces pre- and postsynaptic differentiation of neurons (By
CC similarity). {ECO:0000250|UniProtKB:Q61730,
CC ECO:0000250|UniProtKB:Q9NPH3}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane; Single-pass type I
CC membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Membrane-bound IL-1R AcP;
CC IsoId=P59822-1; Sequence=Displayed;
CC Name=2; Synonyms=Soluble IL-1R AcP;
CC IsoId=P59822-2; Sequence=Not described;
CC -!- DOMAIN: The TIR domain mediates NAD(+) hydrolase (NADase) activity.
CC Self-association of TIR domains is required for NADase activity.
CC {ECO:0000255|PROSITE-ProRule:PRU00204}.
CC -!- SIMILARITY: Belongs to the interleukin-1 receptor family.
CC {ECO:0000305}.
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DR EMBL; AY182233; AAO24704.1; -; mRNA.
DR EMBL; AY182234; AAO24705.1; -; mRNA.
DR RefSeq; NP_001028132.1; NM_001032960.1. [P59822-1]
DR AlphaFoldDB; P59822; -.
DR SMR; P59822; -.
DR STRING; 9544.ENSMMUP00000029702; -.
DR Ensembl; ENSMMUT00000107688; ENSMMUP00000068286; ENSMMUG00000022562. [P59822-1]
DR GeneID; 574387; -.
DR KEGG; mcc:574387; -.
DR CTD; 3556; -.
DR VEuPathDB; HostDB:ENSMMUG00000022562; -.
DR eggNOG; ENOG502QRDG; Eukaryota.
DR GeneTree; ENSGT01050000244913; -.
DR HOGENOM; CLU_025552_1_0_1; -.
DR InParanoid; P59822; -.
DR OMA; KRSHRWS; -.
DR OrthoDB; 985064at2759; -.
DR TreeFam; TF325519; -.
DR Proteomes; UP000006718; Chromosome 2.
DR Bgee; ENSMMUG00000022562; Expressed in liver and 22 other tissues.
DR ExpressionAtlas; P59822; baseline.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004908; F:interleukin-1 receptor activity; IBA:GO_Central.
DR GO; GO:0005149; F:interleukin-1 receptor binding; IBA:GO_Central.
DR GO; GO:0050135; F:NAD(P)+ nucleosidase activity; IEA:UniProtKB-EC.
DR GO; GO:0061809; F:NAD+ nucleotidase, cyclic ADP-ribose generating; IEA:UniProtKB-EC.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IBA:GO_Central.
DR GO; GO:0051965; P:positive regulation of synapse assembly; ISS:UniProtKB.
DR Gene3D; 2.60.40.10; -; 3.
DR Gene3D; 3.40.50.10140; -; 1.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR015621; IL-1_rcpt_fam.
DR InterPro; IPR004074; IL-1_rcpt_I/II-typ.
DR InterPro; IPR041416; IL-1RAcP-like_ig.
DR InterPro; IPR000157; TIR_dom.
DR InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR PANTHER; PTHR11890; PTHR11890; 1.
DR Pfam; PF18452; Ig_6; 1.
DR Pfam; PF01582; TIR; 1.
DR PRINTS; PR01536; INTRLKN1R12F.
DR SMART; SM00409; IG; 3.
DR SMART; SM00255; TIR; 1.
DR SUPFAM; SSF48726; SSF48726; 3.
DR SUPFAM; SSF52200; SSF52200; 1.
DR PROSITE; PS50835; IG_LIKE; 2.
DR PROSITE; PS50104; TIR; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein;
KW Hydrolase; Immunoglobulin domain; Inflammatory response; Membrane; NAD;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; Secreted; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..570
FT /note="Interleukin-1 receptor accessory protein"
FT /id="PRO_0000015451"
FT TOPO_DOM 21..367
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 368..388
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 389..570
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 21..128
FT /note="Ig-like C2-type 1"
FT DOMAIN 136..226
FT /note="Ig-like C2-type 2"
FT DOMAIN 242..350
FT /note="Ig-like C2-type 3"
FT DOMAIN 403..546
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT REGION 69..85
FT /note="Essential for interaction with PTPRD"
FT /evidence="ECO:0000250|UniProtKB:Q61730"
FT REGION 549..570
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 482
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT MOD_RES 557
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NPH3"
FT CARBOHYD 57
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 107
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 111
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 118
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 196
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 209
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 299
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 24..122
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 47..114
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 137..181
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 160..212
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 266..332
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 570 AA; 65393 MW; 9CD78AB1E78DD4C5 CRC64;
MTLLWCVVSL YFYGILQSDA SERCDDWGLD TMRQIQVFED EPARIKCPLF EHFLKFNYST
AHSAGLTLIW YWTRQDRDLE EPINFRLPEN RISKEKDVLW FRPTLLNDTG NYTCMLRNTT
YCSKVAFPLE VVQKDSCFNS PMKLPVHKLY IEYGIQRITC PNVDGYFPSS VKPTITWYMG
CYKIQNFNNV IPEGMNLSFL IAFISNNGNY TCVVTYPENG RTFHLTRTLT VKVVGSPKNA
VPPVIHSPND HVVYEKEPGE ELLIPCTVYF SFLMDSRNEV WWTIDGKKPD DIPIDVTINE
SISHSRTEDE TRTQILSIKK VTSEDLKRSY VCHARSAKGE VAKAATVKQK VPAPRYTVEL
ACGFGATVLL VVILIVVYHV YWLEMVLFYR AHFGTDETIL DGKEYDIYVS YARNAEEEEF
VLLTLRGVLE NEFGYKLCIF DRDSLPGGIV TDETLSFIQK SRRLLVVLSP NYVLQGTQAL
LELKAGLENM ASQGNINVIL VQYKAVKETK VKELKRAKTV LTVIKWKGEK SKYPQGRFWK
QLQVAMPVKK SPRRSSSDEQ GLSYSSLKNV
